The immediate aim of this research is to determine by X-ray crystallographic techniques, utilizing the most recent developments in direct methods of structure determination, the structures of a series of ion transport antibiotics and membrane active polypeptides. Because the functional, physical, and chemical properties of a wide spectrum of biological membranes are well defined, there is reason to believe that knowledge of the exact molecular conformation of molecules that act upon and are present in living membranes will provide the key to a full understanding of membrane function at a molecular level. Using computer graphics and force field energy calculations (1) solid state data concerning complexed and uncomplexed forms of valinomycin, monensin, and other ionophores will be used to model the dynamics of ion capture and release processes, (2) data on angiotensin and alamethicin fragments will be used to generate plausible models for their complete structures, and (3) data on conformational isomers of insulin will be used to model the crystallographically observed random coil to helix transformation of seven residues of the B chain. Radioactive labeling will be used in efforts to identify which complex forms of monensin and A23187 are responsible for transport thru non-polar media. The molecular information revealed by these and related studies will be used to resolve ambiguities in spectral analysis, to advance conceptualization of molecular mechanisms such as hydrogen bond formation, ion solvation, and peptide conformational change, to provide better parameters for force field calculations, and to test the feasibility of present ion transport and membrane structure models. Because membranes through their transport properties can be said to exert some control over almost all cell functions, and because drugs, hormones, and vitamins may have their primary effect upon cell membranes, there is little doubt that a better knowledge of membrane molecular function would contribute substantially to understanding cell function and malfunction.